Prolonged expression of therapeutic levels of human granulocyte colony-stimulating factor in rats following gene transfer to skeletal muscle.

Publication Type:

Journal Article


Human gene therapy, Volume 7, Issue 12, p.1423-9 (1996)


Animals, Cells, Cultured, Child, Preschool, Gene Therapy, Gene Transfer Techniques, Granulocyte Colony-Stimulating Factor, Hematopoiesis, Humans, Leukocyte Count, Male, Muscle, Skeletal, NEUTROPENIA, Neutrophils, Rats, Rats, Inbred F344, Recombinant Fusion Proteins, Time Factors


Gene transfer to skeletal muscle was examined as a means of gene therapy for neutropenia. A recombinant retrovirus containing a human granulocyte colony-stimulating factor (G-CSF) gene was introduced into primary human or rat myoblasts, which were then shown to produce biologically active G-CSF. Transplantation of G-CSF-producing rat myoblasts into the muscle of syngeneic rats resulted in a 15-fold increase in absolute neutrophil counts. This increase correlated with detection of circulating human G-CSF protein throughout the 6-month duration of the experiment. These results clearly demonstrate long-term production of therapeutically relevant amounts of a human protein by normal cells in vivo.